FM-CCUL-Artigos em Revistas Internacionais
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- Vascular function after acute aerobic exercise in adults with and without type 2 diabetes mellitusPublication . Marôco, João Luís; Arrais, Inês; Silvestre, Tiago; Pinto, Marco; Laranjo, Sergio; Magalhães, João P.; Santa-Clara, Helena; Fernhall, Bo; Melo, XavierIt is unknown whether type 2 diabetes mellitus (T2DM) influences the vascular function response to aerobic exercise. We examined brachial artery flow-mediated dilation (FMD) and flow-mediated slowing (FMS) of pulse wave velocity (PWV), 10-and 60-min after a high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in adults with and without T2DM. Twelve older male adults with T2DM (57-84 years), and twenty-four healthy young and older adults (12 per group, aged 20-40 years and 57-76 years, respectively), completed an acute bout of HIIE, MICE, and a non-exercise condition. FMD was evaluated by the same researcher following standardized guidelines. FMS was calculated from the manufacturer's PWV beta formulas. Central arterial stiffness was estimated via carotid-femoral PWV (cfPWV). %FMD was reduced (d= - 5.94%, 95% CI: - 10.50 to - 1.38%, p = 0.002), whereas %FMS increased (d = 4.55%, 95% CI: 0.62 to 8.48%, p = 0.01), 10-min after HIIE only in adults with T2DM, normalizing 60-min into recovery. Conversely, %FMD was increased (d = 5.33%, 95% CI: 0.76 to 9.89%, p = 0.009) 10-min after MICE only in adults with T2DM. cfPWV remained unchanged following HIIE and MICE in all groups. We report disease-associated vascular function responses to aerobic exercise suggesting both HIIE and MICE uncover transient vascular alterations in older adults with T2DM.
- Impairment of spatial working memory but preservation of recognition memory in female rats with spontaneous absence seizuresPublication . Neuparth-Sottomayor, Mariana; Morais, Tatiana P.; Good, Mark; Sebastião, Ana M; Di Giovanni, Giuseppe; Crunelli, Vincenzo; Vaz, Sandra H.Epidemiological studies reveal gender-specific differences in epilepsy. Childhood absence epilepsy (CAE), which is more prevalent in females, is characterized by typical absence seizures (ASs) consisting of brief periods of unconsciousness, associated with 2.5-4 Hz spike-wave discharges (SWDs) in the electroencephalogram (EEG). Children with CAE often present neuropsychological comorbidities, including deficits in attention and executive function. In this study, we investigated anxiety-like behaviour and memory in female Genetic Absence Epilepsy Rat from Strasbourg (GAERS), a validated model of ASs, compared to Non-Epileptic Control (NEC) and Wistar rats. We found that female GAERS generally showed normal anxiety-like behaviour relative to both control strains, although some tests suggested a reduction in anxiety. Importantly, female GAERS showed impaired spatial working memory, while recognition memory was preserved. These findings when compared with previous data in males indicate that while anxiety levels in female GAERS are preserved as those of male GAERS, memory performance differs, with males showing impairments in both spatial working memory and recognition memory. These findings emphasize the importance of considering gender differences in both clinical and preclinical epilepsy research to better understand the neuropsychological comorbidities associates with ASs. This knowledge is crucial for the identification of gender-specific mechanism, as well as the development of gender-sensitive, personalized therapies targeting both seizures and associated cognitive impairments.
- Global impact of fixed-dose combination therapies on cardiovascular mortality and events, 2023-2050: a modeling studyPublication . Watkins, David A.; Pickersgill, Sarah; Flood, David; Gaziano, Thomas A.; Huffman, Mark D.; Islam, Shofiqul; Joseph, Philip; Perel, Pablo; Piñeiro, Daniel J.; Pinto, Fausto J.; Yusuf, SalimBackground: Uptake of drugs for primary and secondary prevention of cardiovascular disease is low in many countries. Single-pill combination (SPC) therapies consisting of a statin and 1 or more antihypertensive drugs, with or without aspirin, can reduce rates of fatal and nonfatal cardiovascular disease, but their use is currently limited. Objectives: The authors modeled the potential impact of widespread adoption of SPC therapies over 2023 to 2050. Methods: We used state-transition and demographic modeling approaches to project ischemic heart disease- and stroke-related deaths and nonfatal events in 182 countries. We modeled the effects of programs to roll out primary and secondary prevention SPCs in 2 scenarios, compared to non-SPC (current) care: 1) targeted strategies to improve adherence and reduce therapeutic inertia among persons already in care; and 2) population-based strategies to provide SPC therapies to most persons at intermediate-to-high risk. We conducted sensitivity analyses around our assumptions on adoption, long-term adherence, and the effect of aspirin. Results: Over 2023-2050, use of SPC therapies could prevent up to 29 million deaths and 51 million cases in the targeted scenario and up to 72 million deaths and 130 million cases in the population scenario. The greatest share of fatal and nonfatal events prevented would be in South and East Asia and the Pacific because of population size. SPC therapies could reduce all-cause premature mortality by 2.0% (targeted) to 3.2% (population), facilitating achievement of global health targets. Conclusions: SPC therapies could substantially accelerate progress on cardiovascular disease mortality by increasing use of preventive drugs, especially in settings where uptake is currently low.
- Predicting the burden for surgical aortic valve replacement in a tertiary centre: the impact of aged populations for the next decadesPublication . Pereira, Rafael Maniés; Carvalho Guerra, Nuno; Moreira Gonçalves, João; Ferreira, Ricardo; Nobre, Angelo; Brito, Dulce; Rodrigues, Teresa Ferreira; Velho, Tiago R.Background/Objectives: The incidence of aortic stenosis (AS) is predicted to rise with the aging population, emerging as a growing public health challenge in developed countries, leading to an increased demand for intervention. Our aim is to predict the evolution of proposed cases for SAVR in the geographic referral area of our tertiary hospital until 2041. Methods: We used data from the Portuguese Census for 2001, 2011, and 2021 to analyze the resident population within the Cardiothoracic Surgery Department's referral area. Applying population projection methods (rate of geometric growth), we projected demographic trends over 20 years, from 2021 to 2041. Our analysis focused on AS cases who underwent SAVR in our department between 2001-2011 and 2011-2021. Results: Between 2001 and 2021, there was an increase in the overall population, particularly among the elderly (1.4% growth rate in the population ≥ 65 years old). The aging index increased from 128.4 (110.5-180.6) in 2001 to 189.1 (155.9-222.5) in 2021 (p-value < 0.001). Similarly, the longevity index significantly increased between 2001 [42.6 (40.8-44.80)] and 2021 [49.30 (47.7-51.8)] (p-value < 0.001). The number of SAVRs performed increased, with a mean increase of 8.11 surgeries/year (R2 = 0.6457, p < 0.001). By 2041, our referral center will increase SAVR by at least 51 surgeries/year in a decreasing growth rate scenario, and 67 surgeries/year in a growth rate stagnation scenario. Conclusions: The ongoing trend of population aging will increase the demand for healthcare resources, particularly within the cardiovascular domain. Accurately assessing the volume of SAVR is imperative for reformulating strategies to address the increasing demand effectively.
- Worsening heart failure: progress, pitfalls, and perspectivesPublication . Fonseca, Cândida; Baptista, Rui; Franco, Fátima; Moura, Brenda; Pimenta, Joana; Moraes Sarmento, Pedro; Cardoso, José Silva; Brito, DulceFor most patients with chronic heart failure (HF), the clinical course of the disease includes periods of apparent clinical stability punctuated by episodes of clinical deterioration with worsening signs and symptoms, a condition referred to as worsening heart failure (WHF). Over time, episodes of WHF may become more frequent, and patients may enter a cycle of recurrent events associated with deterioration in their quality of life and functional capacity, hospitalizations, and ultimately death. WHF is apparently an old concept but seems to have acquired new boundaries in terms of definition and clinical and prognostic value due to the fast-paced evolution of the HF treatment landscape and the emergence of new drugs in this setting. As a result, the management of WHF is being reshaped. In the present paper, a group of HF experts gathered to discuss the concept, prevention, detection, and treatment of WHF.
- Integrating sleep-related breathing disorders and epigenetics into the genetic landscape of sleep disturbances in psychotic disordersPublication . Perdigoto, Susana; De Pedro, Miguel; Meira e Cruz, MiguelRecent advances in psychiatric genetics have underscored the role of polygenic scores (PGSs) in shaping sleep phenotypes in individuals with psychotic disorders. The study by Cederlöf et al. (Reference Cederlöf, Holm, Kämpe, Ahola-Olli, Kantojärvi, Lähteenvuo and Paunio2025) makes an important contribution by leveraging genome-wide association data to disentangle the complex interplay between genetic liability for insomnia, sleep duration, chronotype, and schizophrenia. Their findings offer compelling insights into how distinct genetic risks manifest in both subjective experiences and cognitive performance. Yet, the genetic landscape of sleep in psychosis is even more nuanced than the current framework suggests. Several biologically and clinically relevant dimensions—namely sleep-related breathing disorders (SRBDs), the COMISA phenotype (comorbid insomnia and sleep apnea), and the dynamic influence of epigenetic regulation—warrant deeper integration into this conversation.
- Balloon pulmonary angioplasty and Riociguat in the management of chronic thromboembolic pulmonary hypertension: a systematic reviewPublication . Camões De Araújo, Patrícia; Calé, Rita; Pereira, Ernesto; Ferreira, Filipa; Alegria, Sofia; Pereira, Helder; Coelho, AndréBackground: No systematic review has been published comparing the effectiveness and safety of balloon pulmonary angioplasty (BPA) and riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) across studies that evaluate both treatment methods. Methods: A literature search was conducted using PubMed, ScienceDirect, and Elsevier. Clinical, functional, and hemodynamic effectiveness criteria were analysed, as well as complications related to both interventions. Results: Five studies were reviewed, including randomized clinical trials and observational studies, comprising a total of 184 patients who underwent riociguat and BPA, 94 patients who underwent BPA alone, and 79 who underwent riociguat alone. Patients receiving combination therapy demonstrated a more significant improvement in WHO-FC, PVR, and CO (≈1.13 L/min) compared to monotherapy (BPA: ≈0.45 L/min and riociguat: ≈0.84 L/min). Regarding the 6MWD, patients who started with Riociguat before combination therapy showed a greater improvement (≈78 m) than those on monotherapy (BPA: ≈46.9 m and riociguat: ≈38.2 m). The reduction in mPAP was greater in patients treated with BPA alone (≈-17.6 mmHg) compared to riociguat alone (≈-5.4 mmHg) or combination therapy (≈-12.2 mmHg). In the BPA group, the rate of life-threatening complications was very low, with haemoptysis or pulmonary haemorrhage being the most common adverse events (15 %-44 %). In the riociguat group, dizziness, headaches, gastrointestinal reflux, vomiting, and nausea were reported (15 %-23 %). Among patients undergoing both treatments, the vascular injury rate was <11 %, with the most common adverse event being the need for non-invasive ventilation (30 %). Conclusions: Combination therapy appears to be more effective than monotherapy, without being associated to major adverse events in patients diagnosed with CTEPH.
- Balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertensionPublication . Pereira, Ana Rita; Calé, Rita; Ferreira, Filipa; Pereira, HelderBalloon pulmonary angioplasty (BPA) is an emerging treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual/recurrent pulmonary hypertension after pulmonary thromboendarterectomy. We report two patients with inoperable and severe CTEPH who were submitted to the BPA programme after optimised treatment with long-term oxygen therapy (LTOT) and pulmonary vasodilator drugs, including prostacyclin analogues. They experienced a significant improvement in exercise capacity, oxygenation, right ventricular function and pulmonary haemodynamics. This improvement allowed withdrawal from LTOT and prostacyclin analogues therapies and, consequently, improved patients' quality of life and reduced future health-related costs. The reported clinical cases intend to highlight the effectiveness of BPA in patients with inoperable CTEPH for whom the only available therapy was, until recently, the pulmonary vasodilator drugs.
- Upfront lipid-lowering combination therapy in high cardiovascular risk patients: a route to effectve atherosclerotic cardiovascular disease preventionPublication . Banach, Maciej; Surma, Stanisław; Guzik, Tomasz J.; Penson, Peter E.; Blaha, Michael J.; Pinto, Fausto J.; Sperling, Laurence S.Despite three decades of using statin therapy, 20 years of experience with ezetimbe, and availability of innovative non-statin lipid lowering therapies (LLT), there are still about 70% patients over the low-density lipoprotein cholesterol (LDL-C) goal, with every 5th to 6th being over the target from the group of very high and extremely high cardiovascular disease (CVD) risk patients. Adding another even every 5th patient at very high CVD risk without any LLT makes this situation highly frustrating, especially lipid disorders are the most common CVD risk factor with the prevalence of over 60%, with the worst awareness within all cardiovascular risk factors (only about 15% people knows their LDL-C level). To answer this since 2021, there is an approach to apply upfront (immediate) lipid-lowering combination therapy of statin and ezetimibe in very high and extremely high-risk patients to be on the LDL-C target as low as possible, but especially as early as possible, enabling to introduce the third line therapy (i.e. bempedoic acid and/or PCSK9 targeted therapy) already after 4–6 weeks. This review discusses the current stage of knowledge and recent data on the group of patients that might benefit the most from the upfront combination LLT, when it should be optimally implemented, and the recent data on its role on LDL-C reduction, cardiovascular and mortality outcomes as well as safety issues
- Beyond inflammation: the role of metabolic dysregulation in sepsis diagnosis and treatmentPublication . Payen, Didier; Velho, Tiago R.; Moita, LuisSepsis is a life-threatening organ dysfunction syndrome that results from a dysregulated host response to infection. Our evolving understanding of sepsis pathophysiology now incorporates insights from molecular advances, particularly in the felds of immunity and, more recently, metabolism. The concept that sepsis induces metabolic perturbations is not new. In fact, hyperlactatemia, metabolic acidosis, hypocholesterolaemia, or hyperglycaemia are essential indicators of sepsis severity [2]. Conversely, chronic metabolic conditions may contribute to the severity and type of host response to infection. However, the mechanistic contribution of specifc metabolic pathways to the quality and magnitude of immune responses in sepsis and other conditions that impose signifcant stress on the organism has only recently begun to be explored. In this perspective, we briefy highlight critical aspects of metabolic reprogramming (changes in metabolic pathways to meet diferent energy demands, support growth, adapt to environmental conditions, or survive stress) associated with sepsis. We then explore how knowledge of different metabolic signatures (distinct, measurable profles of metabolites or metabolic activities that characterize a particular biological state, disease, cell type, or response to treatment) may lead to innovative diagnostic and therapeutic approaches.